This project was initiated to study the role of brain neuropeptides in genetic hypertension and stress and was later extended to study the interrelationship between different neuropeptides and their role in neuroendocrine regulation. We took advantage of animal models of disease: the spontaneously hypertensive rat, which in its homozygous state lacks the antidiuretic hormone vasopressin, and presents the syndrome of diabetes insipidus. Spontaneously hypertensive rats show alterations in angiotensin-converting enzyme in peripheral tissues and specific forebrain nuclei. Changes in somatostatin metabolism and in the activity of angiotensin-converting enzyme occur in pituitary gland and specific brain nuclei of Brattleboro rats. Endogenous somatostatin occurs in the pituitary gland, where it is probably present in nerve terminals to the intermediate lobe which originates in the hypothalamus. In the intermediate lobe, somatostatin inhibits the isoproterenol-stimulated adenylate cyclase, and it is probably involved in the release of neuropeptides from this structure.